The tumor marker human placental protein 11 is an endoribonuclease.
Human PP11 (placental protein 11) was previously described as a serine protease specifically expressed in the syncytiotrophoblast and in numerous tumor tissues. Several PP11-like proteins were annotated in distantly related organisms, such as worms and mammals, suggesting their involvement in evolutionarily conserved processes. Based on sequence similarity, human PP11 was included in a protein family whose characterized members are XendoU, a Xenopus laevis endoribonuclease involved in small nucleolar RNA processing, and Nsp15, an endoribonuclease essential for coronavirus replication. Here we show that the bacterially expressed human PP11 displays RNA binding capability and cleaves single stranded RNA in a Mn(2+)-dependent manner at uridylates, to produce molecules with 2',3'-cyclic phosphate ends. These features, together with structural and mutagenesis analyses, which identified the potential active site residues, reveal striking parallels to the amphibian XendoU and assign a ribonuclease function to PP11. This newly discovered enzymatic activity places PP11-like proteins in a completely new perspective.
Laneve
Pietro
P
Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Sapienza Università di Roma, Rome, Italy.
Gioia
Ubaldo
U
Ragno
Rino
R
Altieri
Fabio
F
Di Franco
Carmen
C
Santini
Tiziana
T
Arceci
Massimo
M
Bozzoni
Irene
I
Caffarelli
Elisa
E
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011257:Pregnancy Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry; D014982:Xenopus laevis
D014408:Biomarkers, Tumor; D011257:Pregnancy Proteins; D012330:RNA, Double-Stranded; C036270:placental protein 11; D012313:RNA; D004722:Endoribonucleases